Decrease In Vascular Permeability Research Articles

Suppression by adrenoceptor beta-agonists of vascular permeability increase and edema formation induced by arachidonate metabolites, platelet-activating factor, and tumor-promoting phorbol ester TPA

Air-pouch-type inflammation was induced by injecting sodium carboxymethyl cellulose solution containing leukotriene C4 (LTC4, 3.20 × 10−7 M, 0.2 μg/ml) and prostaglandin E2 (PGE2, 5.68 × 10−6 M, 2.0 μg/ml), platelet-activating factor (PAF, 1 × 10−6 M, 0.52 μg/ml), or 12-O-tetradecanoyl phorbol 13-acetate (TPA, 1.62 × 10−6 M, 1.0 μg/ml) into an air pouch made on the dorsum of rats. Vascular permeability and tissue edema formation were significantly increased by injecting the phlogogen solution. The histamine level in the pouch fluid was dramatically increased by injecting TPA but not by LTC4 and PGE2, or PAF. Injection of isoproterenol or procaterol with the phlogogen solution produced dose-dependent suppression of both vascular permeability increase and tissue edema formation. However, the TPA-induced increase in the histamine level was not suppressed in parallel with the decrease of vascular permeability or tissue edema formation. These results indicate that beta-agonists suppress vascular permeability response and local tissue edema formation not by inhibiting mast cell degranulation, but by inhibiting the reactivity of the local vasculature to chemical mediators such as arachidonate metabolites, PAF, and histamine and serotonin released from mast cells.

Functional and structural evaluation of the vasculature of skin flaps after ischemia and reperfusion.

Free radicals and other toxic oxygen species play a role in the pathogenesis of ischemic organ damage. The abdominal skin flap has been used as a model to study the effects of superoxide dismutase on the survival of ischemic skin. We have evaluated the evolution of functional and structural injury to the vasculature after ischemic injury in superoxide dismutase-treated and control skin flaps. Ischemia was induced by creating abdominal skin flaps and occluding either the venous or both the venous and arterial blood supplies. Superoxide dismutase was administered immediately after the occlusion was released. At 1 hour of reflow, erythrocyte stasis, platelet deposition, neutrophil adherence, and injury to the endothelium of the large vessels and of the microvasculature were evident. The blood flow in the ischemic skin was only 3 percent of normal. Superoxide dismutase caused no change in the ultrastructure of the vasculature and a marginal decrease in vascular permeability in the ischemic skin at 1 hour of reflow. Increased fluorescent staining of the skin was evident after 24 hours of reflow in the superoxide dismutase-treated flaps. These findings indicate that injury to vascular endothelium by ischemia and reperfusion plays a role in the evolution of skin necrosis.

Effects of photosensitizer (hematoporphyrin derivative-HPD) and light dose on vascular targets in the albino mouse ear.

Photodynamic damage to normal tissues, including skin, appears to occur by photooxidative damage to the normal microvasculature as the primary target sensitized by HPD bound to the vascular wall or endothelial cell. Initial damage to the microvasculature was measured by the increase in vascular permeability (VP) as measured by Evans Blue dye (EB) extravasation as a function of HPD and laser light (632 nm) dose. Albino, Swiss-Webster mice (female 122-25 g, 5 mice per group) were injected intraperitoneally (IP) with incremental doses of HPD (Photofrin II, Photofrin Medical, Inc.) (1, 10, 20, 30, 40 and 50 mg/kg). After 48 hours the left ear of each mouse was masked as a control and the right ear was irradiated at 632 nm using the Aurora-Lexel Argon-dye laser (Cooper Laser Sonics, Inc.) with an intensity of 50 mW/cm2 and light doses of 0, 25, 50, 75, and 100 J/cm2 directed to a 3-mm spot on the mouse ear. No EB leakage occurred in the absence of HPD at any light dose or in the absence of light at any HPC dose. Vascular permeability increased as a function of HPD dose up to 30 mg/kg. AT 50 mg/kg HPD, there was a decrease in VP. At each HPD dose above 10 mg/kg, the VP increased as a function of light dose up to 75 J/cm2. Further increase in light dose was without effect. The amount of HPD porphyrin recovered from irradiated ears decreased as a function of light dose. There appeared to be an irreversible photo destruction of the porphyrin exposed to light.

Dynamic changes of fenestrations in choriocapillaries.

The ultrastructure of choriocapillaries from dark-adapted eyes of Uroloncha Striata Domestica was studied with a freeze-fracture replica technique. Fenestrations were observed on the surface of the cleavage plane of the choriocapillary endothelial membrane. Fenestrations of endothelial cells facing Bruch's membrane in controls were densely distributed and clearly separated from the non-fenestrated areas. The average diameter of the fenestrations was 71±6 nm and the average number of fenestrations was 39.1±6.0/μm2. In the dark-adapted eye, the fenestrations of endothelial cells facing Bruch's membrane were scattered and it was impossible to clearly distinguish the fenestrated areas from non-fenestrated areas. The average diameter of the fenestrations was 70±6 nm and the average number of fenestrations was 27.4±7.6/μm2. The difference in fenestration density between control and adapted eyes was significant (P<0.01). These findings indicate that the distribution pattern of fenestrations in endothelial cells of choriocapillaries is dynamic and results in a decrease in vascular permeability of the choriocapillaries in the dark.

Desensitization to locally injected PGF 2α as reflected in the vascular permeability and collagen and noncollagenous protein synthesis of carrageenin-induced granulation tissue in rats

Administration of PGF 2α at doses of 50 and 250 μg into pouch fluid (calculated concentration of PGF 2α was about 4 and 14 μg/ml of pouch fluid, respectively) of 7-day-old carrageenin granuloma in rats depressed vascular permeability, as measured by leakage of radioiodinated human serum albumin into the pouch fluid. However, 3 hr after PGF 2α treatment at a dose of 50 μg. the vascular permeability had recovered to control level; 3 hr after a dose of 250 μg PGF 2α, the vascular permeability had not recovered completely. The uptake of [ 3H]proline into collagen hydroxyproline and noncollagenous protein of carrageenin granuloma tissue was also examined. It was found that the first injection of PGF2a at a dose of 50 or 250 μg depressed the uptake of [ 3H]proline into both protein fractions, but 3 hr after the first injection of PGF 2α, there was no significant difference in uptake between the control and the PGF 2α-treated group. A study of the metabolism of PGF 2α in a homogenate of granulation tissue and in pouch fluid showed little activity in the former and very little activity in the latter. In the homogenate, about 70 per cent of the originally added [ 3H]PGF 2α remained unmetabolized after 3 hr of incubation. In the inflammatory fluid, less than 20 per cent of the radioactivity present at 35 min after the injection had dissappeared from the pouch fluid at 3 hr after the [ 3H]PGF 2α injection; all the remaining radioactivity was found to be unmetabolized [ 3H]PGF 2α. Consequently, it was suggested that the tissue became desensitized to the injected PGF 2α. To confirm this suggestion, another 50 or 250 μg of PGF 2α was injected 3 hr after the first PGF 2α injection. However, a decrease in vascular permeability and in uptake of [ 3H]proline into both protein fractions after the second injection of PGF 2α were not observed. It was concluded that, 3 hr after the first PGF 2α treatment, the sensitivity of the carrageenin-induced granulation tissue to PGF 2α had decreased.